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Degarelix

Also known as: Firmagon, FE200486, degarelix acetate, GnRH antagonist (synthetic decapeptide)

GnRH receptor antagonist — synthetic decapeptide; androgen deprivation therapy (ADT) agent

Research chemicalLast updated: October 10, 2026Based on 6 peer-reviewed studiesPreclinical data only — no human trials
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What it is

Degarelix (Firmagon) is a monthly injection used in men with advanced prostate cancer to shut down testosterone production — the fuel that drives most prostate cancers. Unlike older hormone-blocking drugs, it works immediately without the temporary worsening of symptoms that can occur at the start of treatment. FDA-approved since 2008.

The scientific side

degarelix is a synthetic decapeptide that acts as a competitive antagonist at pituitary gonadotropin-releasing hormone (GnRH) receptors, directly blocking receptor activation without any initial stimulatory effect. This mechanistic distinction from GnRH agonists (such as leuprolide, goserelin, and triptorelin) is clinically critical: GnRH agonists paradoxically cause a transient testosterone surge during the first 1–2 weeks of treatment due to pituitary receptor stimulation before desensitization, which can temporarily worsen symptoms including bone pain, urinary obstruction, or spinal cord compression. Degarelix eliminates this testosterone flare entirely by occupying GnRH receptors competitively, preventing LH and FSH release from the outset. In the pivotal Phase III trial (n=610), subcutaneous degarelix (240 mg loading, then 80 mg every 28 days) suppressed serum testosterone to castrate levels (≤0.5 ng/mL) by day 3 in the vast majority of patients — median castrate testosterone was achieved within 72 hours — compared with day 28 for leuprolide recipients. Testosterone suppression was sustained at 97.2% and 98.3% of patients in the two degarelix maintenance dose groups across 12 months, meeting non-inferiority versus leuprolide. PSA suppression also occurred more rapidly with degarelix. Beyond testosterone suppression, emerging evidence from a translational study (n=49 primary prostate cancers; PMID 39269310) shows that degarelix-induced androgen deprivation transforms the prostate tumor microenvironment within days, increasing activated CD8+ T cells, expanding proinflammatory M1-like tumor-associated macrophages, upregulating tumor MHC class I and II antigen presentation, and downregulating the 'do not eat me' signal CD47 — findings with implications for combination immunotherapy strategies. The Cochrane systematic review (11 RCTs; PMID 34350976) confirmed that degarelix likely results in little to no difference in overall survival versus standard GnRH agonist therapy, with lower rates of musculoskeletal events and PSA progression noted in some analyses.

Class: GnRH receptor antagonist — synthetic decapeptide; androgen deprivation therapy (ADT) agent

Administration & storage

Administration
Subcutaneous injection into the abdominal area only (not the waistband or belt areaperiumbilical areaor areas with pressure from clothing)Loading dose requires two separate 120 mg SC injections administered consecutively at different sites in the abdominal regionInjection should be given slowly into a pinched skin fold at a 45-degree angleSite rotation within the abdominal region is recommended for each subsequent injection
Storage
Unopened vials: store at controlled room temperature 25°C (77°F); excursions permitted to 15–30°C. Do not freeze. Reconstituted solution should be used immediately and not stored. Protect from light.
Cautions
Injection site reactions (ISRs) are the most commonly reported adverse effect: pain, erythema, swelling, induration, and warmth at the injection site. Reported in 40% of patients in Phase III. ISRs are generally transient and mild-to-moderate. Three-month depot formulation (480 mg) causes significantly more intense ISRs than monthly 80 mg.,QT/QTc interval prolongation: GnRH agonists and antagonists, including degarelix, can prolong the QT interval. Use with caution in patients with known QT prolongation, electrolyte abnormalities, or concomitant QT-prolonging medications.,Cardiovascular risk: All ADT agents reduce testosterone, which can increase cardiovascular risk over time (metabolic effects, dyslipidemia, insulin resistance). PRONOUNCE trial did not demonstrate a cardiovascular advantage for degarelix over leuprolide in patients with established ASCVD (MACE: 5.5% degarelix vs. 4.1% leuprolide; HR 1.28, p=0.53).,Testosterone flare absent: Unlike GnRH agonists, degarelix does not cause an initial testosterone surge. This is the key safety advantage for patients with imminent spinal cord compression, severe bone pain, or acute urinary obstruction.,Bone mineral density: Long-term testosterone suppression with any ADT agent causes bone loss. Bone density monitoring and consideration of bisphosphonates or denosumab are recommended for patients on extended ADT.,Hepatic enzyme elevations: Transaminase elevations have been reported. Liver function monitoring is advised in patients with pre-existing hepatic disease.,Hypersensitivity reactions: Anaphylaxis, urticaria, and angioedema have been reported post-marketing. Degarelix is contraindicated in patients with known hypersensitivity to degarelix or any excipient.

Legal & regulatory status

US FDA

FDA-approved (NDA 022201) as Firmagon (degarelix for injection) for treatment of advanced prostate cancer. Approved December 2008. Administered as subcutaneous injection: 240 mg loading dose followed by 80 mg…

WADA

Degarelix is prohibited under the WADA Prohibited List. GnRH antagonists, including degarelix, fall under Section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics) and are prohibited both…

Health Canada

Approved in Canada as Firmagon for treatment of advanced hormone-sensitive prostate cancer. Regulatory approval aligns with the EU and US class approvals for GnRH antagonists in ADT. Listed as a Schedule F prescription…